Crystal structure of 2-[(5-amino-1-tosyl-1H-pyrazol-3-yl)oxy]-1-(4-methoxyphenyl)ethan-1-one 1,4-dioxane monosolvate

In the molecular structure of the title compound, the pyrazole and its oxy-ethanone substituent lie parallel to each other, whereas the sulfonyl ring is roughly perpendicular to the pyrazole. The residues form a layer structure by hydrogen bonding.

In the structure of the title compound, C 19 H 19 N 3 O 5 S•C 4 H 8 O 2 , the two independent dioxane molecules each display inversion symmetry.The pyrazole ring is approximately parallel to the aromatic ring of the oxy-ethanone group and approximately perpendicular to the tolyl ring of the sulfonyl substituent.An extensive system of classical and 'weak' hydrogen bonds connects the residues to form a layer structure parallel to (201), within which dimeric subunits are conspicuous; neighbouring layers are connected by classical hydrogen bonds to dioxanes and by 'weak' hydrogen bonds from H tolyl donors.

Chemical context
We are currently developing several synthetic strategies for the preparation of new heterocyclic compounds containing Nsulfonylamino-and N-sulfonyl moieties, which have recently been shown to possess significant biological activity as novel anti-covid-19, antimicrobial and antiviral agents (Azzam et al., 2019;Elgemeie et al., 2019Elgemeie et al., , 2022;;Zhu et al., 2013).Some of our recently reported N-arylsulfonylpyrazoles (Elgemeie et al., 1998(Elgemeie et al., , 2002(Elgemeie et al., , 2013) ) have been used by other groups as inhibitors of NS2B-NS3 virus and cathepsin B16 (Myers et al., 2007;Sidique et al., 2009).In this context, we are seeking simple and innovative syntheses for other new derivatives of N-sulfonated pyrazoles, in the hope of finding different scaffolds for use as promising future drugs (Zhang et al., 2020).
We have previously prepared both N-alkylated (Metwally et al., 2021a) and O-alkylated (Metwally et al., 2021b) derivatives of N-tosylpyrazole 1.In order to determine which factors lead to the formation of N-alkylated or O-alkylated products of Ntosylpyrazole, a reaction (Fig. 1) was conducted of N-tosylpyrazole (1) with 2-bromo-1-(4-methoxyphenyl)ethan-1-one (2) and potassium carbonate in dry N,N-dimethylformamide at room temperature.This yielded an adduct for which two isomeric structures are possible, the O-alkylated or N-alkylated N-tosylpyrazoles 3 or 4. The 1 H NMR spectrum of the product showed five singlet signals at � = 2.37, 3.85, 4.92, 5.42 and 6.31 ppm, assigned to the CH 3 , OCH 3 , CH-pyrazole, CH 2 and NH 2 protons, respectively, in addition to signals from the aromatic protons.The formation of a mixture could thereby be excluded.The X-ray structure determination unambiguously confirmed the formation of the O-alkylated N-sulfonylpyrazole 4. The synthesis of this product rather than the isomeric N-tosylpyrazole 3 might be attributable to the possibility that 4 is the thermodynamically controlled product because of less steric hindrance.

Structural commentary
The structure of compound 4 (as its 1,4-dioxane solvate 4 0 ) is shown in Fig. 2, where the dioxane rings, which lie around inversion centres, have been completed by symmetry.The dioxanes containing O81 and O91 are henceforth referred to as dioxanes 1 and 2 respectively.A selection of molecular dimensions is given in Table 1; these may be considered as normal.The atom sequence C5-C4-C3-O2-C2-C1-C11-C12 is characterized by torsion angles close to �180 � ; the greatest deviation from antiperiplanar values is seen for C3-O2-C2-C1 at À 166.35 (3) � .This extended antiperiplanar sequence causes the heterocycle and the ring at C11 to be approximately parallel, whereas the heterocycle and the tolyl rings are approximately perpendicular to each other [interplanar angles of 7.58 (3) and 82.92 (1) � , respectively].An intramolecular hydrogen bond N3-H032� � �O4 is formed from an amino hydrogen atom to a sulfonyl oxygen atom (Table 2).The nitrogen atom N3 of the amine group is somewhat pyramidalized; N3 lies 0.177 (5) A ˚outside the plane of C5, H031 and H032, and the angle sum at N3 is 350.2 � .

Supramolecular features
For details of hydrogen bonds, see Table 2. Within the asymmetric unit (Fig. 2), dioxane 1 is connected to the molecule of 4 by a classical hydrogen bond N3-H031� � �O81, which is part of a three-centre system; the other branch is the intramolecular N3-H032� � �O4.Dioxane 2 is connected by the 'weak' hydrogen bond C17-H17B� � �O91 (henceforth, we The structure of compound 4 0 in the crystal.Both dioxane molecules display inversion symmetry; only the asymmetric unit is numbered.Ellipsoids represent 50% probability levels.Dashed lines indicate hydrogen bonds.See also the Refinement section.

Table 1
Selected geometric parameters (A ˚, � ).Reaction scheme for the synthesis of 4.

research communications
Acta Cryst.(2024).E80, 29-33 Figure 4 The hydrogen-bonded dimeric unit of compound 4 0 .Classical and 'weak' hydrogen bonds are indicated by thick and thin dashed lines respectively.Hydrogen atoms not involved in these hydrogen bonds are omitted for clarity.Radii are arbitrary.

Figure 5
A ribbon of connected dimers of compound 4 0 , viewed perpendicular to (201), with dioxanes 2, which link to the neighbouring ribbons (not shown).Atoms that connect the dimeric units are labelled.Dioxanes 1 are omitted.

Database survey
The search employed the routine ConQuest (Bruno et al., 2002), part of Version 2022.3.0 of the Cambridge Database (Groom et al., 2016).
A search for pyrazole structures with the same substitution pattern as 4 (i.e. S at N1, O at C3, N at C5) gave only one hit (apart from 5), namely 5-amino-1-[(4-fluorophenyl)sulfonyl]-1H-pyrazol-3-yl thiophene-2-carboxylate (refcode YILPUF; Myers et al., 2007), in which only the O-substituent differs significantly from that of 4. Analogously to 4, the thiophene ester group is approximately parallel to, and the sulfonate ring perpendicular to, the pyrazole ring.The packing of the solvent-free structure involves hydrogen bonds of the type N-H� � �O sulfonyl and N-H� � �N2 pyrazole , which link the molecules by translation to form a ribbon structure.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Hydrogen atoms of the NH 2 group were refined freely, but with N-H distances restrained to be approximately equal (command 'SADI').The methyl groups were included as idealized rigid groups allowed to rotate but not tip (command 'AFIX 137 0 , with C-H = 0.98 A ˚, H-C-H = 109.5� ; all methyl hydrogens, even those of the tosyl group, were shown clearly in the circular difference-density map).Other hydrogen atoms were included using a riding model starting from calculated positions (C-H aromatic = 0.95 A ˚, C-H methylene = 0.99 A ˚).The U iso (H) values were fixed at 1.5 � U eq of the parent carbon atoms for the methyl group and 1.2 � U eq for other hydrogens.A total of six badly fitting reflec-tions (with |error/esd| > 9.25) were removed from the refinement with 'OMIT' commands.
Both dioxane sites involve inversion centres.The dioxane site 2 was slightly disordered, with an occupation factor of 0.069 (2) for the minor component; in the sections above, only the major component is discussed.To improve refinement stability, appropriate restraints were employed (commands 'SIMU' and 'SAME'), but the dimensions of disordered groups should always be interpreted with caution.Furthermore, the assignment of O and C atoms to the minor site should be regarded as tentative.In Fig. 2 the dioxane 2 is centred on 0, 0.5, 0. To show its hydrogen bond H17B� � �O91, 2 would need to be transformed to a position centred on 0, 1.5, 0, which lies outside the unit cell.(Sheldrick, 2015b), SHELXL2019/3 (Sheldrick, 2015a) and XP (Siemens, 1994).

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å gave an r.m.s.deviation of 0.21 A ˚; the ring orientation of the tosyl ring is the poorest fit [cf.N1-S1-C21-C22 torsion angle of 101.19 (3) � in 4 0 compared to 111.54 (3) � for the corresponding angle in 5].

Figure 6
Figure 6Packing of compound 4 0 viewed edge-on to the layer structure (projected parallel to the b axis; the layers lie horizontally), thus showing the role of the dioxanes 1 and the hydrogen bond H25� � �O6 in bridging the layers.Hydrogen bonds H27A� � �O3, which also connect the layers, are not shown; they are formed at the points where C27 of one layer projects into the next layer and lie almost parallel to the view direction.

Table 3
Experimental details.